Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT.
Stem Cell Res Ther
; 11(1): 256, 2020 06 26.
Article
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| MEDLINE
| ID: mdl-32586403
ABSTRACT
BACKGROUND:
MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma.METHODS:
MSCTRAIL were radiolabelled with 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo.RESULTS:
MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections.CONCLUSIONS:
89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Tomografía Computarizada por Tomografía de Emisión de Positrones
/
Neoplasias Pulmonares
Idioma:
En
Revista:
Stem Cell Res Ther
Año:
2020
Tipo del documento:
Article